The three areas of research proposed share a common objective; to define precisely the mechanisms of solute and water transport across nephron fragments perfused in vitro. Preliminary data from rabbit descending limbs perfused at low pressure indicate that the water permeability of this segment is about 1/200th the published value. The urea permeability of these low pressure tubules appears to be high. Measurement of solute permeability of both thin limbs of henle and tests to determine the nature of preferential solute reabsorption in the thin ascending limb are planned for tubules perfused at low pressure. These data will be used to test the validity of current models for counter-current multiplication. Aldosterone may stimulate active sodium transport across the in vitro rabbit collecting tubule by 1) stimulating the entry step at the luminal membrane, 2) stimulating the sodium "pump" itself at the peritubular membrane, 3) or both. Experiments designed to test and quantitate the functions of these membrane processes are proposed. A miniature AG-AgCl electrode, developed in this laboratory, can be used to voltage clamp segments of the amphibian nephron in vitro. This electrode will be used to test current hypotheses on the mechanism of active chloride transport across the diluting segment. (This amphibian nephron segment is functionally similar to the mammalian thick accending limb of Henle). Voltage clamp experiments designed to study the nature of K ion transport across the amphibian distal nephron are proposed. It is anticipated that each of the proposed areas of research will contribute substantially to our knowledge of renal function.